Different Sugars Have Different Effects on Brain

Glucose appears to tamper brain activity in regions that regulate appetite and reward -- but fructose does not, a new study found.

The brain imaging study found participants who had a drink sweetened with glucose had reduced blood flow in an area of the brain called the hypothalamus, while those who drank a fructose-sweetened beverage saw a slight increase in blood flow -- a proxy for brain activity -- Dr. Robert Sherwin of Yale University and colleagues reported in the Jan. 2 issue of the Journal of the American Medical Association.

Glucose also reduced activation in the insula and striatum, other brain regions that regulate appetite, motivation, and reward processing, while fructose did not, the researchers wrote.

In an accompanying editorial, Dr. Jonathan Purnell and Damien Fair of Oregon Health and Science University in Portland, said the findings "support the conceptual framework that when the human brain is exposed to fructose, neurobiological pathways involved in appetite regulation are modulated, thereby promoting increased food intake."

As the obesity epidemic has grown, so too has consumption of fructose in the American diet, the researchers explained in their article. Fructose is found in both sucrose, or table sugar, and in high-fructose corn syrup, another common sweetener. It is valued because it's sweeter than glucose.

But studies show fructose may have different metabolic effects than glucose. For instance, fructose only weakly stimulates secretion of insulin, a hormone that can increase satiety, and attenuates levels of the satiety hormone glucagon-like peptide-1 (GLP-1) -- so researchers are concerned that it could possibly increase food-seeking behavior and intake.

To assess those effects, Sherwin and colleagues conducted functional MRIs (fMRIs) in 20 normal-weight, healthy adults who were given 75 grams of either glucose or fructose in a cherry-flavored drink, and then crossed over to a drink with the other sweetener.

Participants rated their feelings of hunger, satiety, and fullness before and after the scan, and the researchers took blood to assess circulating hormone levels.

Overall, the researchers found that glucose significantly reduced cerebral blood flow in the hypothalamus, while fructose did not. Specifically, blood flow fell 5.45 mL/g per minute from baseline with glucose, compared with an increase of 2.84 mL/g per minute with fructose, for a mean difference of 8.3 ml/g per minute, they found.

They also found that glucose reduced cerebral blood flow in the thalamus, insula, anterior cingulate, and striatum -- "regions that act in concert to 'read' the metabolic state of an individual and drive motivation and reward" -- compared with baseline.

In contrast, fructose reduced blood flow in the hippocampus, posterior cingulate cortex, fusiform, and visual cortex -- but also in the thalamus.

In terms of connectivity between brain regions, glucose upped the links between the hypothalamus and the thalamus and striatum, while fructose only increased connectivity between the hypothalamus and thalamus, but not the striatum -- the latter of which also de-activates once a person is sated, the researchers said.

"These findings suggest that ingestion of glucose, but not fructose, initiates a coordinated response between the homeostatic-striatal network that regulates feeding behavior," they wrote.